Cancer is a leading cause of death in most countries, and the result of billions of dollars in healthcare expense around the world. It is now well established that a variety of cancers are caused, at least in part, by genetic abnormalities that result in either the overexpression of cancer causing genes, called “oncogenes,” or from loss of function mutations in protective genes, often called “tumor suppressor” genes. One of the main obstacles in clinical oncology is that tumors can usually resist therapy, leading to tumor regrowth and even metastasis. There are many reasons that may explain why tumor cells become resistant to anti-cancer drugs, such as the ability of tumor cells to undergo selection for acquired resistance.
It has been demonstrated that several types of bone marrow derived cells home-in on chemotherapy-treated tumors and colonize there, leading to increased angiogenesis and metastasis.
The contribution of host cells to tumor growth is not solely dependent on angiogenesis. Recent studies indicated that immune cells, such as macrophages, also related to as tumor associated macrophages (TAMs) contribute to tumor growth. Macrophages are myeloid cells that are linked with inflammation. There are two main phenotypes of macrophages: M1 and M2. These two phenotypes are associated not only with tumors, but also with other pathological and physiological conditions related to the inflammatory cascade. During the inflammatory process M1 macrophages initially arrive and colonize the damaged tissue. They secrete various cytokines and chemokines at the inflammatory site, which ignite the inflammatory cascade. M1 macrophages have high phagocytotic properties and they secrete pro-inflammatory factors. On the other hand, M2 macrophages colonize the inflammatory tissue only a few days after M1 macrophages colonized the tissue. Their role is to stop the inflammatory process, and to initiate a regeneration process. Therefore, they secrete anti-inflammatory cytokines and growth factors known to repair damaged tissue, among those are factors promoting cell proliferation, migration, and activation. In cancer, M2 macrophages were found to substantially contribute to the tumorigenesis process and to metastasis, while M1 macrophages most likely contribute to the inhibition of pro-tumorigenic properties of cancer cells by creating an acute inflammatory process.
IL-31 is an immunoregulatory cytokine that is mainly produced by activated Th2 cells. IL-31 acts through the heterodimeric receptors of IL-31 (IL-31R) and oncostatin M receptor (OSMR), which are expressed on IL-31 activated monocytes and on epithelial cells.
The possible role of IL-31 as an anti-cancer compound was not investigated as of to date.
There is a need in identifying a new treatment for cancer.